A group of structurally related benzonaphthofurans showed differential growth inhibitory activity against a number of melanoma, breast, and selected other human tumor cell lines in the NCI primary in vitro anticancer drug screen. The goal of this project was to develop analytical methods for the assay of the most potent of these analogs in plasma and to define their in vivo pharmacokinetic properties. This information will be used to provide an objective basis for selecting the most promising candidate for in vivo tumor inhibition studies and to optimize the design of in vivo efficacy studies. Intravenous and oral pharmacokinetic studies have been completed to date on three of the benzonaphthofurans. These include two compounds with phenolic hydroxyls (NSC 649250D and NSC 653483D) and an analog with no hydroxyl substituent (NSC 644904D). Following IV injection of 10 mg/kg to mice, plasma concentration-time profiles of the phenolic compounds exhibited biexponential behavior, while the analog without a hydroxyl substituent exhibited triexponential behavior. Initial half-lives were rapid for all three compounds, ranging from 1 to 7 minutes, indicating rapid distribution into the tissues. The terminal half-lives of the analogs containing an hydroxyl group, 24 and 13 minutes respectively, were substantially shorter than that for the analog without this functional group (122 minutes). The plasma total body clearance for all three compounds was very high, ranging from 126 ml/min/kg (NSC 649250D) to 302 ml/min/kg (NSC 644904D). The very high total body volume of distribution for the compound having no phenolic group (55 l/kg) suggests that it is extensively distributed into deep tissue compartments. The total body volumes of distribution for the analogs containing the hydroxyl group, 8 and 2 l/kg respectively, while indicating high tissue distribution, were much lower than that of the congener which was not a phenol. Following oral administration of 50 mg/kg, the oral bioavailability of NSC 644904D was 25%. The oral bioavailability of the analogs containing the hydroxyl group, on the other hand, were very low, 7% and 4%, respectively. Conclusions regarding the optimum candidates of this series will be derived when the pharmacokinetic studies have been completed.